The fabrication of artificial receptors that can achieve recognition at the molecular level is one of the major goals of organic and bio-organic chemistry. Based on the increasing understanding of the basic interactions (hydrogen bonding, ionic interaction, hydrophobic effect, metal chelating, etc.) between molecules and the recognition between substrate-enzyme, antigen-antibody and ligand-receptor, several well known synthetic recognition systems have been developed.sup.1, and newly synthesized receptors are rapidly emerging.sup.2.
Molecular imprinting is a technique for the preparation of such artificial receptors, separation materials of high specificity, artificial enzymes and other synthetic members of a ligand binding pair.sup.3-6. Molecular imprinted polymer (MIP) materials prepared by molecular imprinting have been successfully used for chiral separation of amino acid derivatives.sup.7, drugs.sup.8, sugar derivatives.sup.9, specific recognition of steroids.sup.10, proteins and protein analogues .sup.11, as antibody and receptor mimics.sup.12, as ion selective absorbents.sup.13 and as enzyme mimics to direct organic reactions.sup.14-17.
Generally, MIPs are prepared by polymerization in a relatively non-polar solvent exhibiting better recognition sites than those prepared using a polar solvent. Better recognition sites are also expected using templates having more noncovalent interacting groups. However, one common problem is that many such compounds are normally not very soluble in nonpolar organic solvents. Because of this, the development of a method for making good MIPs in polar organic solvents is of general interest.
Currently, the carboxyl group is the most commonly used hydrogen bonding functional group. Although it can form strong ionic interactions with basic functional groups, the hydrogen bonding ability of this functional group is not very strong in polar solvents. Often MIPs made in a polar solvent containing carboxyl groups which can only form hydrogen bond interactions with the print molecule exhibit weak recognition, and in some cases no recognition at all.sup.7c,d,18.
Although amide monomers have not been reported as components of MIPs, previous results reported that a polymer imprinted against a template having an amide group instead of an ester group normally gave much better enantiomeric resolution.sup.7a,b.19,20. In addition, amide monomers have also been used in templates in combination with different functional monomers. For templates having both hydrogen bonding and acidic functional groups, the combination of methyacrylic acid and a basic functional monomer (vinyl pyridine) was shown to give MIPs improved enantiomeric recognition.sup.7d. One obvious problem with this combination is that the ionic interaction between these two functional monomers might decrease the imprinting efficiency.
U.S. Pat. No. 5,541,342 refers to the preparation of molecular imprints using polymers of L-proline and methacrylic acid amide. The amide group, however, becomes part of the linking group to the proline and is not available to participate in bonding to the print molecule. Rather, as in other prior art MIPS, non-covalent bonding of the print molecule occurs through carboxyl groups, in this case provided by the prolines.